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FAM20A mutations can cause enamel-renal syndrome (ERS).

Wang SK, Aref P, Hu Y, Milkovich RN, Simmer JP, El-Khateeb M, Daggag H, Baqain ZH, Hu JC - PLoS Genet. (2013)

Bottom Line: Enamel-renal syndrome (ERS) is an autosomal recessive disorder characterized by severe enamel hypoplasia, failed tooth eruption, intrapulpal calcifications, enlarged gingiva, and nephrocalcinosis.By characterizing teeth extracted from the family 3 proband, we demonstrated that FAM20A(-/-) molars lacked true enamel, showed extensive crown and root resorption, hypercementosis, and partial replacement of resorbed mineral with bone or coalesced mineral spheres.Supported by the observation of severe ectopic calcifications in the kidneys of Fam20a mice, we conclude that FAM20A, which has a kinase homology domain and localizes to the Golgi, is a putative Golgi kinase that plays a significant role in the regulation of biomineralization processes, and that mutations in FAM20A cause both AIGFS and ERS.

View Article: PubMed Central - PubMed

Affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.

ABSTRACT
Enamel-renal syndrome (ERS) is an autosomal recessive disorder characterized by severe enamel hypoplasia, failed tooth eruption, intrapulpal calcifications, enlarged gingiva, and nephrocalcinosis. Recently, mutations in FAM20A were reported to cause amelogenesis imperfecta and gingival fibromatosis syndrome (AIGFS), which closely resembles ERS except for the renal calcifications. We characterized three families with AIGFS and identified, in each case, recessive FAM20A mutations: family 1 (c.992G>A; g.63853G>A; p.Gly331Asp), family 2 (c.720-2A>G; g.62232A>G; p.Gln241_Arg271del), and family 3 (c.406C>T; g.50213C>T; p.Arg136* and c.1432C>T; g.68284C>T; p.Arg478*). Significantly, a kidney ultrasound of the family 2 proband revealed nephrocalcinosis, revising the diagnosis from AIGFS to ERS. By characterizing teeth extracted from the family 3 proband, we demonstrated that FAM20A(-/-) molars lacked true enamel, showed extensive crown and root resorption, hypercementosis, and partial replacement of resorbed mineral with bone or coalesced mineral spheres. Supported by the observation of severe ectopic calcifications in the kidneys of Fam20a mice, we conclude that FAM20A, which has a kinase homology domain and localizes to the Golgi, is a putative Golgi kinase that plays a significant role in the regulation of biomineralization processes, and that mutations in FAM20A cause both AIGFS and ERS.

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Related in: MedlinePlus

Backscatter Scanning Electron Micrographs (bSEMs) of molar (#32).A: The bSEM of molar after it was cut sagitally (mesial-distally). B: Rough “enamel” (e) covering sclerotic dentin. C: Acellular cementum covering sclerotic root dentin. D–E: Highly mineralized pulp or radicular calcifications (pc) comprised of coalesced spheres above the root furcation and associated with a less mineralized material that contacts dentin (d). F: The radicular area appears to be comprised entirely of acellular cementum (ac) or lamellar bone from the furcation to the highly mineralized coalesced spheres. G: Root dentin covered with a thick layer of acellular cementum (ac) or bone. A thin line of more highly mineralized material, possibly cementum (c), separates these layers. H: The material covering root dentin is deposited in layers and sometimes fills in areas of localized root resorption.
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pgen-1003302-g011: Backscatter Scanning Electron Micrographs (bSEMs) of molar (#32).A: The bSEM of molar after it was cut sagitally (mesial-distally). B: Rough “enamel” (e) covering sclerotic dentin. C: Acellular cementum covering sclerotic root dentin. D–E: Highly mineralized pulp or radicular calcifications (pc) comprised of coalesced spheres above the root furcation and associated with a less mineralized material that contacts dentin (d). F: The radicular area appears to be comprised entirely of acellular cementum (ac) or lamellar bone from the furcation to the highly mineralized coalesced spheres. G: Root dentin covered with a thick layer of acellular cementum (ac) or bone. A thin line of more highly mineralized material, possibly cementum (c), separates these layers. H: The material covering root dentin is deposited in layers and sometimes fills in areas of localized root resorption.

Mentions: An unerupted third molar (#32) was also characterized by bSEM and showed a somewhat different pattern of pathological resorption and mineralization (Figure 11). The “enamel” layer was very thin, rough, and discontinuous. It was more highly mineralized than dentin in most places, and appeared to have coalesced from multiple mineral foci. The dentin had well-organized dentinal tubules. The pulp was partially calcified. Besides major resorption of dentin from part of the root surface, the bulk of the pathology was in the furcation area, which included a large hypermineralized region of coalesced calcospherites surrounded by lamellar bone that extended coronally to the pulp and apically beyond the furcation so that the bone-like material seems to have entirely replaced the dentin at the furcation but retained the original morphology of the furcation.


FAM20A mutations can cause enamel-renal syndrome (ERS).

Wang SK, Aref P, Hu Y, Milkovich RN, Simmer JP, El-Khateeb M, Daggag H, Baqain ZH, Hu JC - PLoS Genet. (2013)

Backscatter Scanning Electron Micrographs (bSEMs) of molar (#32).A: The bSEM of molar after it was cut sagitally (mesial-distally). B: Rough “enamel” (e) covering sclerotic dentin. C: Acellular cementum covering sclerotic root dentin. D–E: Highly mineralized pulp or radicular calcifications (pc) comprised of coalesced spheres above the root furcation and associated with a less mineralized material that contacts dentin (d). F: The radicular area appears to be comprised entirely of acellular cementum (ac) or lamellar bone from the furcation to the highly mineralized coalesced spheres. G: Root dentin covered with a thick layer of acellular cementum (ac) or bone. A thin line of more highly mineralized material, possibly cementum (c), separates these layers. H: The material covering root dentin is deposited in layers and sometimes fills in areas of localized root resorption.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585120&req=5

pgen-1003302-g011: Backscatter Scanning Electron Micrographs (bSEMs) of molar (#32).A: The bSEM of molar after it was cut sagitally (mesial-distally). B: Rough “enamel” (e) covering sclerotic dentin. C: Acellular cementum covering sclerotic root dentin. D–E: Highly mineralized pulp or radicular calcifications (pc) comprised of coalesced spheres above the root furcation and associated with a less mineralized material that contacts dentin (d). F: The radicular area appears to be comprised entirely of acellular cementum (ac) or lamellar bone from the furcation to the highly mineralized coalesced spheres. G: Root dentin covered with a thick layer of acellular cementum (ac) or bone. A thin line of more highly mineralized material, possibly cementum (c), separates these layers. H: The material covering root dentin is deposited in layers and sometimes fills in areas of localized root resorption.
Mentions: An unerupted third molar (#32) was also characterized by bSEM and showed a somewhat different pattern of pathological resorption and mineralization (Figure 11). The “enamel” layer was very thin, rough, and discontinuous. It was more highly mineralized than dentin in most places, and appeared to have coalesced from multiple mineral foci. The dentin had well-organized dentinal tubules. The pulp was partially calcified. Besides major resorption of dentin from part of the root surface, the bulk of the pathology was in the furcation area, which included a large hypermineralized region of coalesced calcospherites surrounded by lamellar bone that extended coronally to the pulp and apically beyond the furcation so that the bone-like material seems to have entirely replaced the dentin at the furcation but retained the original morphology of the furcation.

Bottom Line: Enamel-renal syndrome (ERS) is an autosomal recessive disorder characterized by severe enamel hypoplasia, failed tooth eruption, intrapulpal calcifications, enlarged gingiva, and nephrocalcinosis.By characterizing teeth extracted from the family 3 proband, we demonstrated that FAM20A(-/-) molars lacked true enamel, showed extensive crown and root resorption, hypercementosis, and partial replacement of resorbed mineral with bone or coalesced mineral spheres.Supported by the observation of severe ectopic calcifications in the kidneys of Fam20a mice, we conclude that FAM20A, which has a kinase homology domain and localizes to the Golgi, is a putative Golgi kinase that plays a significant role in the regulation of biomineralization processes, and that mutations in FAM20A cause both AIGFS and ERS.

View Article: PubMed Central - PubMed

Affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.

ABSTRACT
Enamel-renal syndrome (ERS) is an autosomal recessive disorder characterized by severe enamel hypoplasia, failed tooth eruption, intrapulpal calcifications, enlarged gingiva, and nephrocalcinosis. Recently, mutations in FAM20A were reported to cause amelogenesis imperfecta and gingival fibromatosis syndrome (AIGFS), which closely resembles ERS except for the renal calcifications. We characterized three families with AIGFS and identified, in each case, recessive FAM20A mutations: family 1 (c.992G>A; g.63853G>A; p.Gly331Asp), family 2 (c.720-2A>G; g.62232A>G; p.Gln241_Arg271del), and family 3 (c.406C>T; g.50213C>T; p.Arg136* and c.1432C>T; g.68284C>T; p.Arg478*). Significantly, a kidney ultrasound of the family 2 proband revealed nephrocalcinosis, revising the diagnosis from AIGFS to ERS. By characterizing teeth extracted from the family 3 proband, we demonstrated that FAM20A(-/-) molars lacked true enamel, showed extensive crown and root resorption, hypercementosis, and partial replacement of resorbed mineral with bone or coalesced mineral spheres. Supported by the observation of severe ectopic calcifications in the kidneys of Fam20a mice, we conclude that FAM20A, which has a kinase homology domain and localizes to the Golgi, is a putative Golgi kinase that plays a significant role in the regulation of biomineralization processes, and that mutations in FAM20A cause both AIGFS and ERS.

Show MeSH
Related in: MedlinePlus